methyl 5-bromo-4-oxopentanoate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of methyl 5-bromo-4-oxopentanoate (2.51 g, 12.0 mmol), 1-(5-bromo-3-phenoxypyridin-2-yl)thiourea (3.00 g, 9.25 mmol), triethylamine (2.19 mL, 15.7 mmol), and ethanol (60 mL) was refluxed for 3 hours and then stirred at ambient temperature overnight. The solvent was removed to about one third original volume and partitioned between CH2Cl2 and water. The organics were concentrated and purified on silica gel eluting with 40% EtOAc/Hexanes to give the title compound (3.22 g, 80.1% yield). was refluxed for 3 hours The solvent was removed to about one third original volume partitioned between CH2Cl2 and water The organics were concentrated purified on silica gel eluting with 40% EtOAc/Hexanes

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of bromine (27.71 g, 173.4 mmol) in methanol (40 mL) was added dropwise to a solution of ethyl 4-oxopentanoate (25.0 g, 173.4 mmol) in methanol (200 mL) at room temperature over a period of 30 minute, and the reaction mixture was stirred overnight. The reaction mixture was concentrated, and the residue was partitioned between 3:1 ether:ethyl acetate and water, washed with saturated sodium bicarbonate, water, brine, dried, and concentrated to afford 17 g of a crude clear oil. The oil was purified by MPLC (Biotage) eluting with 8:1 hexane ethyl acetate to afford methyl 5-bromo-4-oxopentanoate (10.65 g, 29.38% yield) as a clear oil. 1H NMR (CDCl3) δ 3.96 (s, 2H), 3.69 (s, 3H), 2.96 (t, 2H), 2.66 (t, 2H). The reaction mixture was concentrated the residue was partitioned between 3:1 ether ethyl acetate and water, washed with saturated sodium bicarbonate, water, brine dried concentrated to afford 17 g of a crude clear oil The oil was purified by MPLC (Biotage) eluting with 8:1 hexane ethyl acetate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of methyl 5-bromo-4-oxopentanoate (2.51 g, 12.0 mmol), 1-(5-bromo-3-phenoxypyridin-2-yl)thiourea (3.00 g, 9.25 mmol), triethylamine (2.19 mL, 15.7 mmol), and ethanol (60 mL) was refluxed for 3 hours and then stirred at ambient temperature overnight. The solvent was removed to about one third original volume and partitioned between CH2Cl2 and water. The organics were concentrated and purified on silica gel eluting with 40% EtOAc/Hexanes to give the title compound (3.22 g, 80.1% yield). was refluxed for 3 hours The solvent was removed to about one third original volume partitioned between CH2Cl2 and water The organics were concentrated purified on silica gel eluting with 40% EtOAc/Hexanes

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of methyl 5-bromo-4-oxopentanoate (2.51 g, 12.0 mmol), 1-(5-bromo-3-phenoxypyridin-2-yl)thiourea (3.00 g, 9.25 mmol), triethylamine (2.19 mL, 15.7 mmol), and ethanol (60 mL) was refluxed for 3 hours and then stirred at ambient temperature overnight. The solvent was removed to about one third original volume and partitioned between CH2Cl2 and water. The organics were concentrated and purified on silica gel eluting with 40% EtOAc/Hexanes to give the title compound (3.22 g, 80.1% yield). was refluxed for 3 hours The solvent was removed to about one third original volume partitioned between CH2Cl2 and water The organics were concentrated purified on silica gel eluting with 40% EtOAc/Hexanes

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of bromine (27.71 g, 173.4 mmol) in methanol (40 mL) was added dropwise to a solution of ethyl 4-oxopentanoate (25.0 g, 173.4 mmol) in methanol (200 mL) at room temperature over a period of 30 minute, and the reaction mixture was stirred overnight. The reaction mixture was concentrated, and the residue was partitioned between 3:1 ether:ethyl acetate and water, washed with saturated sodium bicarbonate, water, brine, dried, and concentrated to afford 17 g of a crude clear oil. The oil was purified by MPLC (Biotage) eluting with 8:1 hexane ethyl acetate to afford methyl 5-bromo-4-oxopentanoate (10.65 g, 29.38% yield) as a clear oil. 1H NMR (CDCl3) δ 3.96 (s, 2H), 3.69 (s, 3H), 2.96 (t, 2H), 2.66 (t, 2H). The reaction mixture was concentrated the residue was partitioned between 3:1 ether ethyl acetate and water, washed with saturated sodium bicarbonate, water, brine dried concentrated to afford 17 g of a crude clear oil The oil was purified by MPLC (Biotage) eluting with 8:1 hexane ethyl acetate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of bromine (27.71 g, 173.4 mmol) in methanol (40 mL) was added dropwise to a solution of ethyl 4-oxopentanoate (25.0 g, 173.4 mmol) in methanol (200 mL) at room temperature over a period of 30 minute, and the reaction mixture was stirred overnight. The reaction mixture was concentrated, and the residue was partitioned between 3:1 ether:ethyl acetate and water, washed with saturated sodium bicarbonate, water, brine, dried, and concentrated to afford 17 g of a crude clear oil. The oil was purified by MPLC (Biotage) eluting with 8:1 hexane ethyl acetate to afford methyl 5-bromo-4-oxopentanoate (10.65 g, 29.38% yield) as a clear oil. 1H NMR (CDCl3) δ 3.96 (s, 2H), 3.69 (s, 3H), 2.96 (t, 2H), 2.66 (t, 2H). The reaction mixture was concentrated the residue was partitioned between 3:1 ether ethyl acetate and water, washed with saturated sodium bicarbonate, water, brine dried concentrated to afford 17 g of a crude clear oil The oil was purified by MPLC (Biotage) eluting with 8:1 hexane ethyl acetate

反応条件: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 40 g quantity of 3,4-diethoxybenzamide and 80 g of methyl 5-bromo-4-oxopentanoate (containing about 35% of methyl 3-bromo-4-oxopentanoate) were added to 400 ml of dimethylformamide, and the mixture was stirred at 130° C. for 16 hours. The reaction mixture was concentrated under reduced pressure and diluted with ethyl acetate. Ethyl acetate (500 ml) and saturated sodium bicarbonate solution (500 ml) were gradually added with stirring, and stirring was continued. The organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=1:8 to 1:4) to give 18 g of white powdery methyl 3-[2-(3,4-diethoxyphenyl)oxazol-4-yl]propionate. The reaction mixture was concentrated under reduced pressure diluted with ethyl acetate Ethyl acetate (500 ml) and saturated sodium bicarbonate solution (500 ml) were gradually added with stirring stirring The organic layer was dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=1:8 to 1:4)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 100 ml of a 1M methanolic sodium thiophenolate solution there was added 22 g (0.1 mole) 5-bromo-4-oxo-valeric acid methylester during 40 minutes and the reaction mixture was stirred for two hours at room temperature. The methanol was distilled off in vacuo, to the residue there was added 200 ml ethyl acetate, and the mixture was washed successively with 30 water, 30 ml sodium bicarbonate solution, 30 ml saturated saline solution, then dried over magnesium sulfate, filtered, and the solvent was distilled off. The residue was chromatographed on a column using a 4:1 mixture of hexane and ethyl acetate as an eluent. The methanol was distilled off in vacuo, to the residue there was added 200 ml ethyl acetate the mixture was washed successively with 30 water, 30 ml sodium bicarbonate solution, 30 ml saturated saline solution dried over magnesium sulfate filtered the solvent was distilled off The residue was chromatographed on a column a 4:1 mixture of hexane and ethyl acetate as an eluent

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of methyl 5-bromo-4-oxopentanoate (2.51 g, 12.0 mmol), 1-(5-bromo-3-phenoxypyridin-2-yl)thiourea (3.00 g, 9.25 mmol), triethylamine (2.19 mL, 15.7 mmol), and ethanol (60 mL) was refluxed for 3 hours and then stirred at ambient temperature overnight. The solvent was removed to about one third original volume and partitioned between CH2Cl2 and water. The organics were concentrated and purified on silica gel eluting with 40% EtOAc/Hexanes to give the title compound (3.22 g, 80.1% yield). was refluxed for 3 hours The solvent was removed to about one third original volume partitioned between CH2Cl2 and water The organics were concentrated purified on silica gel eluting with 40% EtOAc/Hexanes

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of methyl 5-bromo-4-oxopentanoate (2.51 g, 12.0 mmol), 1-(5-bromo-3-phenoxypyridin-2-yl)thiourea (3.00 g, 9.25 mmol), triethylamine (2.19 mL, 15.7 mmol), and ethanol (60 mL) was refluxed for 3 hours and then stirred at ambient temperature overnight. The solvent was removed to about one third original volume and partitioned between CH2Cl2 and water. The organics were concentrated and purified on silica gel eluting with 40% EtOAc/Hexanes to give the title compound (3.22 g, 80.1% yield). was refluxed for 3 hours The solvent was removed to about one third original volume partitioned between CH2Cl2 and water The organics were concentrated purified on silica gel eluting with 40% EtOAc/Hexanes

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of bromine (27.71 g, 173.4 mmol) in methanol (40 mL) was added dropwise to a solution of ethyl 4-oxopentanoate (25.0 g, 173.4 mmol) in methanol (200 mL) at room temperature over a period of 30 minute, and the reaction mixture was stirred overnight. The reaction mixture was concentrated, and the residue was partitioned between 3:1 ether:ethyl acetate and water, washed with saturated sodium bicarbonate, water, brine, dried, and concentrated to afford 17 g of a crude clear oil. The oil was purified by MPLC (Biotage) eluting with 8:1 hexane ethyl acetate to afford methyl 5-bromo-4-oxopentanoate (10.65 g, 29.38% yield) as a clear oil. 1H NMR (CDCl3) δ 3.96 (s, 2H), 3.69 (s, 3H), 2.96 (t, 2H), 2.66 (t, 2H). The reaction mixture was concentrated the residue was partitioned between 3:1 ether ethyl acetate and water, washed with saturated sodium bicarbonate, water, brine dried concentrated to afford 17 g of a crude clear oil The oil was purified by MPLC (Biotage) eluting with 8:1 hexane ethyl acetate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of bromine (27.71 g, 173.4 mmol) in methanol (40 mL) was added dropwise to a solution of ethyl 4-oxopentanoate (25.0 g, 173.4 mmol) in methanol (200 mL) at room temperature over a period of 30 minute, and the reaction mixture was stirred overnight. The reaction mixture was concentrated, and the residue was partitioned between 3:1 ether:ethyl acetate and water, washed with saturated sodium bicarbonate, water, brine, dried, and concentrated to afford 17 g of a crude clear oil. The oil was purified by MPLC (Biotage) eluting with 8:1 hexane ethyl acetate to afford methyl 5-bromo-4-oxopentanoate (10.65 g, 29.38% yield) as a clear oil. 1H NMR (CDCl3) δ 3.96 (s, 2H), 3.69 (s, 3H), 2.96 (t, 2H), 2.66 (t, 2H). The reaction mixture was concentrated the residue was partitioned between 3:1 ether ethyl acetate and water, washed with saturated sodium bicarbonate, water, brine dried concentrated to afford 17 g of a crude clear oil The oil was purified by MPLC (Biotage) eluting with 8:1 hexane ethyl acetate